Prevalence of Alcohol Consumption and Hazardous Drinking, Tobacco and Drug use in urban Tanzania, and Their associated Risk Factors.

Evidence suggests substance abuse in Tanzania is a growing public health problem. A random sample of 899 adults aged 15-59 in two urban sites of differing levels of poverty surveyed alcohol, tobacco and illicit substance use. Rates of substance use were 17.2%. 8.7% and 0.8% for alcohol, tobacco and cannabis, respectively. Living in the less affluent area was associated with higher lifetime rates of tobacco and alcohol use. Substance use is less prevalent in Tanzania than in richer countries, but lifetime consumption is higher in poorer areas. The association of substance use with a range of socio-economic factors warrants further research

Rural to Urban Migration and Changes in Cardiovascular risk Factors in Tanzania: A Prospective Cohort Study.

High levels of rural to urban migration are a feature of most African countries. Our aim was to investigate changes, and their determinants, in cardiovascular risk factors on rural to urban migration in Tanzania. Men and women (15 to 59 years) intending to migrate from Morogoro rural region to Dar es Salaam for at least 6 months were identified. Measurements were made at least one week but no more than one month prior to migration, and 1 to 3 monthly after migration. Outcome measures included body mass index, blood pressure, fasting lipids, and self reported physical activity and diet. One hundred and three men, 106 women, mean age 29 years, were recruited and 132 (63.2%) followed to 12 months. All the figures presented here refer to the difference between baseline and 12 months in these 132 individuals. Vigorous physical activity declined (79.4% to 26.5% in men, 37.8% to 15.6% in women, p < 0.001), and weight increased (2.30 kg men, 2.35 kg women, p < 0.001). Intake of red meat increased, but so did the intake of fresh fruit and vegetables. HDL cholesterol increased in men and women (0.24, 0.25 mmoll-1 respectively, p < 0.001); and in men, not women, total cholesterol increased (0.42 mmoll-1, p = 0.01), and triglycerides fell (0.31 mmoll-1, p = 0.034). Blood pressure appeared to fall in both men and women. For example, in men systolic blood pressure fell by 5.4 mmHg, p = 0.007, and in women by 8.6 mmHg, p = 0.001. The lower level of physical activity and increasing weight will increase the risk of diabetes and cardiovascular disease. However, changes in diet were mixed, and may have contributed to mixed changes in lipid profiles and a lack of rise in blood pressure. A better understanding of the changes occurring on rural to urban migration is needed to guide preventive measures

Hydatidiform moles among patients with incomplete abortion in Mwanza City, North western Tanzania

Background: Prevalence of hydatidiform mole is not clearly defined, partly because most studies have reported different prevalence rates from different regions. However, there is no previous study that has determined the prevalence and associated risk factors of HM among patients with incomplete abortion evacuated at Bugando Medical Centre (BMC) and Sekou Toure Regional Hospital (STRH).Methods: A total of 180 patients with incomplete abortion were enrolled between February 2013 and April 2013. The products of conception were collected and analyzed using Haemotoxylin and Eosin staining technique for hydatidiform moles.Results: One hundred and eighty patients with incomplete abortion scheduled for uterine evacuation agreed to participate in this study. The overall prevalence of HM was 12.8%. Majority of patients (27.5%) with HM were those aged below 20 years. No significant association was observed with risk factors such as parity, contraceptive use, previous abortion and blood group.Conclusion: The prevalence of HM (12.8%) was high and age between 15-20 years was the only significant associated risk factor with the presence of HM among patients with incomplete abortion. Therefore, we recommend submission of evacuated products of conception for histopathological analysis to minimize missed opportunity.Keywords: Prevalence, hydatidiform mole, incomplete abortion, Mwanza, Tanzania

Causes of Perinatal Death at a Tertiary Care Hospital in Northern Tanzania 2000-2010: A Registry Based Study.

Perinatal mortality reflects maternal health as well as antenatal, intrapartum and newborn care, and is an important health indicator. This study aimed at classifying causes of perinatal death in order to identify categories of potentially preventable deaths. We studied a total of 1958 stillbirths and early neonatal deaths above 500 g between July 2000 and October 2010 registered in the Medical Birth Registry and neonatal registry at Kilimanjaro Christian Medical Centre (KCMC) in Northern Tanzania. The deaths were classified according to the Neonatal and Intrauterine deaths Classification according to Etiology (NICE). Overall perinatal mortality was 57.7/1000 (1958 out of 33 929), of which 1219 (35.9/1000) were stillbirths and 739 (21.8/1000) were early neonatal deaths. Major causes of perinatal mortality were unexplained asphyxia (n=425, 12.5/1000), obstetric complications (n=303, 8.9/1000), maternal disease (n=287, 8.5/1000), unexplained antepartum stillbirths after 37 weeks of gestation (n= 219, 6.5/1000), and unexplained antepartum stillbirths before 37 weeks of gestation (n=184, 5.4/1000). Obstructed/prolonged labour was the leading condition (251/303, 82.8%) among the obstetric complications. Preeclampsia/eclampsia was the leading cause (253/287, 88.2%) among the maternal conditions. When we excluded women who were referred for delivery at KCMC due to medical reasons (19.1% of all births and 36.0% of all deaths), perinatal mortality was reduced to 45.6/1000. This reduction was mainly due to fewer deaths from obstetric complications (from 8.9 to 2.1/1000) and maternal conditions (from 8.5 to 5.5/1000). The distribution of causes of death in this population suggests a great potential for prevention. Early identification of mothers at risk of pregnancy complications through antenatal care screening, teaching pregnant women to recognize signs of pregnancy complications, timely access to obstetric care, monitoring of labour for fetal distress, and proper newborn resuscitation may reduce some of the categories of deaths

Patient-derived glioblastoma cells show significant heterogeneity in treatment responses to the inhibitor-of-apoptosis-protein antagonist birinapant.

BACKGROUND: Resistance to temozolomide (TMZ) greatly limits chemotherapeutic effectiveness in glioblastoma (GBM). Here we analysed the ability of the Inhibitor-of-apoptosis-protein (IAP) antagonist birinapant to enhance treatment responses to TMZ in both commercially available and patient-derived GBM cells. METHODS: Responses to TMZ and birinapant were analysed in a panel of commercial and patient-derived GBM cell lines using colorimetric viability assays, flow cytometry, morphological analysis and protein expression profiling of pro- and antiapoptotic proteins. Responses in vivo were analysed in an orthotopic xenograft GBM model. RESULTS: Single-agent treatment experiments categorised GBM cells into TMZ-sensitive cells, birinapant-sensitive cells, and cells that were insensitive to either treatment. Combination treatment allowed sensitisation to therapy in only a subset of resistant GBM cells. Cell death analysis identified three principal response patterns: Type A cells that readily activated caspase-8 and cell death in response to TMZ while addition of birinapant further sensitised the cells to TMZ-induced cell death; Type B cells that readily activated caspase-8 and cell death in response to birinapant but did not show further sensitisation with TMZ; and Type C cells that showed no significant cell death or moderately enhanced cell death in the combined treatment paradigm. Furthermore, in vivo, a Type C patient-derived cell line that was TMZ-insensitive in vitro and showed a strong sensitivity to TMZ and TMZ plus birinapant treatments. CONCLUSIONS: Our results demonstrate remarkable differences in responses of patient-derived GBM cells to birinapant single and combination treatments, and suggest that therapeutic responses in vivo may be greatly affected by the tumour microenvironment

Hydatidiform moles among patients with incomplete abortion in Mwanza City, North western Tanzania

Background: Prevalence of hydatidiform mole is not clearly defined, partly because most studies have reported different prevalence rates from different regions. However, there is no previous study that has determined the prevalence and associated risk factors of HM among patients with incomplete abortion evacuated at Bugando Medical Centre (BMC) and Sekou Toure Regional Hospital (STRH). Methods: A total of 180 patients with incomplete abortion were enrolled between February 2013 and April 2013. The products of conception were collected and analyzed using Haemotoxylin and Eosin staining technique for hydatidiform moles. Results: One hundred and eighty patients with incomplete abortion scheduled for uterine evacuation agreed to participate in this study. The overall prevalence of HM was 12.8%. Majority of patients (27.5%) with HM were those aged below 20 years. No significant association was observed with risk factors such as parity, contraceptive use, previous abortion and blood group. Conclusion: The prevalence of HM (12.8%) was high and age between 15-20 years was the only significant associated risk factor with the presence of HM among patients with incomplete abortion. Therefore, we recommend submission of evacuated products of conception for histopathological analysis to minimize missed opportunity

A novel enhancer regulates MGMT expression and promotes temozolomide resistance in glioblastoma

Temozolomide (TMZ) was used for the treatment of glioblastoma (GBM) for over a decade, but its treatment benefits are limited by acquired resistance, a process that remains incompletely understood. Here we report that an enhancer, located between the promoters of marker of proliferation Ki67 (MKI67) and O6-methylguanine-DNA-methyltransferase (MGMT) genes, is activated in TMZ-resistant patient-derived xenograft (PDX) lines and recurrent tumor samples. Activation of the enhancer correlates with increased MGMT expression, a major known mechanism for TMZ resistance. We show that forced activation of the enhancer in cell lines with low MGMT expression results in elevated MGMT expression. Deletion of this enhancer in cell lines with high MGMT expression leads to a dramatic reduction of MGMT and a lesser extent of Ki67 expression, increased TMZ sensitivity, and impaired proliferation. Together, these studies uncover a mechanism that regulates MGMT expression, confers TMZ resistance, and potentially regulates tumor proliferation

XPO1-inhibitor Selinexor induces MGMT expression by activating PKA-CREB signaling in IDH wildtype glioblastoma

PurposeThe temozolomide (TMZ) resistance mechanisms in MGMT-promoter methylated IDH wildtype glioblastoma (GBM) tumors are poorly known. This study aimed to identify potential modulators of TMZ resistance in methylated GBM cells.MethodsA genome-wide shRNA library screen was conducted to identify genes modulating resistance in a TMZ-resistant model of MGMT-methylated U251 GBM cells. The Incucyte Device was used for live cell growth monitoring, and DNA damage was assessed by foci staining.ResultsExportin (XPO1) was among the identified candidate TMZ-resistant genes, and the XPO1 inhibitor Selinexor was selected for further investigations. The MGMT-unmethylated GBM6 cells were sensitive to Selinexor alone, without additional sensitization when combined with TMZ. In contrast, MGMT-methylated GBM22 cells were relatively sensitive to Selinexor alone and were significantly sensitized to the Selinexor/TMZ combination. Interestingly, silencing MGMT sensitized GBM6 cells to the combined Selinexor/TMZ treatment, while forced exogenous MGMT expression blocked the sensitivity of U251 cells to the combined Selinexor/TMZ treatment. Selinexor treatment induced MGMT expression concurrently with increased phosphorylation of serine 133 of CREB protein (pCREBS133) in GBM6 and other MGMT-promoter unmethylated GBM cells. Finally, Selinexor-induced MGMT expression and pCREBS133 were blocked by the protein kinase A inhibitor H89, suggesting a role for PKA-CREB signaling in this process.ConclusionsThis study demonstrates XPO1 as a mediator TMZ resistance in MGMT-methylated GBM cells, and that MGMT expression status is a potential determinant of sensitivity to Selinexor/TMZ treatment in GBM cells. These findings also uncover a novel mechanism linking Selinexor with PKA-CREB-mediated MGMT expression, suggesting that Selinexor may enhance MGMT-dependent TMZ resistance in GBM

Low utilization of health care services following screening for hypertension in Dar es Salaam (Tanzania): a prospective population-based study

Drug therapy in high-risk individuals has been advocated as an important strategy to reduce cardiovascular disease in low income countries. We determined, in a low-income urban population, the proportion of persons who utilized health services after having been diagnosed as hypertensive and advised to seek health care for further hypertension management. A population-based survey of 9254 persons aged 25-64 years was conducted in Dar es Salaam. Among the 540 persons with high blood pressure (defined here as BP >or= 160/95 mmHg) at the initial contact, 253 (47%) had high BP on a 4th visit 45 days later. Among them, 208 were untreated and advised to attend health care in a health center of their choice for further management of their hypertension. One year later, 161 were seen again and asked about their use of health services during the interval. Among the 161 hypertensive persons advised to seek health care, 34% reported to have attended a formal health care provider during the 12-month interval (63% public facility; 30% private; 7% both). Antihypertensive treatment was taken by 34% at some point of time (suggesting poor uptake of health services) and 3% at the end of the 12-month follow-up (suggesting poor long-term compliance). Health services utilization tended to be associated with older age, previous history of high BP, being overweight and non-smoking, but not with education or wealth. Lack of symptoms and cost of treatment were the reasons reported most often for not attending health care. Low utilization of health services after hypertension screening suggests a small impact of a patient-centered screen-and-treat strategy in this low-income population. These findings emphasize the need to identify and address barriers to health care utilization for non-communicable diseases in this setting and, indirectly, the importance of public health measures for primary prevention of these diseases

Oral health behavior patterns among Tanzanian university students: a repeat cross-sectional survey

PURPOSE: This study examines oral health behavioral trends and the development of sociodemographic differences in oral health behaviors among Tanzanian students between 1999 and 2000. METHODS: The population targeted was students attending the Muhimbili University College of Health Sciences (MUCHS) at the University of Dar es Salaam (UDSM), Dar es Salaam, Tanzania. Cross-sectional surveys were conducted and a total of 635 and 981 students, respectively, completed questionnaires in 1999 and 2001. RESULTS: Cross-tabulation analyses revealed that in 1999, the rates of abstinence from tobacco use, and of soft drink consumption, regular dental checkups, and intake of chocolate/candy were 84%, 51%, 48%, and 12%, respectively, among students of urban origin and 83%, 29%, 37%, and 5% among their rural counterparts. The corresponding rates in 2001 were 87%, 56%, 50%, and 9% among urban students and 84%, 44%, 38%, and 4% among rural ones. Multiple logistic regression analyses controlling for sex, age, place of origin, educational level, year of survey, and their interaction terms revealed a significant increase in the rate of soft drink consumption, implementation of oral hygiene measures, and abstinence from tobacco use between 1999 and 2001. Social inequalities observed in 1999, with urban students being more likely than their rural counterparts to take soft drinks and go for regular dental checkups, had leveled off by 2001. CONCLUSION: This study provides initial evidence of oral health behavioral trends, that may be utilized in the planning of preventive programs among university students in Tanzania